Department of Microbiology and Immunology, Indiana University School of Medicine-Terre Haute, Terre Haute, Indiana, United States of America.
Department of Biology, Indiana State University, Terre Haute, Indiana, United States of America.
PLoS One. 2023 Mar 8;18(3):e0282347. doi: 10.1371/journal.pone.0282347. eCollection 2023.
Chitin, a polysaccharide, is ubiquitously found in nature and has been known to be an active immunogen in mammals, and interacts with Toll-like, mannose and glucan receptors, to induce cytokine and chemokine secretions. FIBCD1 is a tetrameric type II transmembrane endocytic vertebrate receptor that binds chitin, is found in human lung epithelium and modulates lung epithelial inflammatory responses to A. fumigatus cell wall polysaccharides. We previously reported the detrimental role of FIBCD1 in a murine model of pulmonary invasive aspergillosis. However, the effect that chitin and chitin-containing A. fumigatus conidia exerts on lung epithelium following exposure through FIBCD1 is not yet fully explored. Using both in vitro and in vivo strategies, we examined how lung and lung epithelial gene expression are modified after exposure to fungal conidia or chitin fragments in the presence or absence of FIBCD1. FIBCD1 expression was associated with a decrease in inflammatory cytokines with increasing size of chitin (dimer-oligomer). Thus, our results demonstrate that FIBCD1 expression modulates cytokine and chemokine expression in response to A. fumigatus conidia that is modified by the presence of chitin particles.
几丁质是一种多糖,广泛存在于自然界中,已知是哺乳动物中的一种活性免疫原,与 Toll 样受体、甘露糖受体和葡聚糖受体相互作用,诱导细胞因子和趋化因子的分泌。FIBCD1 是一种四聚体 II 型跨膜内吞脊椎动物受体,与几丁质结合,存在于人肺上皮细胞中,并调节肺上皮细胞对烟曲霉细胞壁多糖的炎症反应。我们之前报道了 FIBCD1 在肺侵袭性曲霉菌病的小鼠模型中的有害作用。然而,几丁质和含几丁质的烟曲霉分生孢子暴露于 FIBCD1 后对肺上皮的影响尚未完全探索。我们使用体内和体外策略,研究了在存在或不存在 FIBCD1 的情况下,暴露于真菌分生孢子或几丁质片段后,肺和肺上皮的基因表达如何发生变化。FIBCD1 的表达与炎症细胞因子的减少有关,随着几丁质(二聚体-低聚物)的大小增加而减少。因此,我们的结果表明,FIBCD1 的表达调节对烟曲霉分生孢子的细胞因子和趋化因子表达,而这种表达受几丁质颗粒的存在所修饰。